Under the conditions of intensive pig-rearing, post weaning colibacillosis is ubiquitous. For example, intensive pig-rearing is used throughout Europe, the United States and Australia. For example, in the United States, post-weaning colibacillosis is the most common cause of mortality in the weaner pig (Leman et al., 1986). The disease is associated with the proliferation of Escherichia coli bacteria in the anterior small intestine after weaning, and gives rise to either death, or the young weaner failing to make normal weight-gains. Other microbiological diseases are common and often accompany colibacillosis in pigs as well as in other animals in intensive rearing conditions, especially poultry.
In the past, attempts have been made to control disease by the ingestion of antimicrobial compositions or by vaccination, neither of which has proved entirely effective.
The rationale behind the lack of success surrounding ingestion of antimicrobial compositions has been the fact that proteinaceous feedstuffs and the contents of the gastrointestinal tract present a reactive and hazardous environment to any chemotherapeutic agent and hence, in vitro active antimicrobial agent will often not be effective when used in vivo within the gastrointestinal tract.
Further, to be antimicrobially effective in a practical way, there is often the restrictive demand that the gastrointestinal disease controlling agent should reasonably maintain the very low microbiological content in the duodenum, yet the very high content in the lower parts of the intestine.
As well, it does not follow that even in vivo effective antimicrobials will give weight-gains, since it is common that even a cocktail of several such commercially used antimicrobials only gives rise to variable, partial or even negative relative weight-gains over control animals.
Accordingly, there is a need for improvements in the prevention and/or treatment of disease via ingestion of antimicrobial compositions in humans and/or animals and/or birds in need of said treatment. Furthermore, there is the need for the attainment of weight gains of said humans and/or animals and/or birds undergoing said treatment.
The present invention provides polymers and/or copolymers preferably derived from acrolein and having the polymeric repeating unit:
wherein R is H or alkyl, usually C1 to C4 or this unit in hydrated, hemiacetal or acetal form and illustrated non-comprehensively of all possible structures, by the following formulae:
wherein n is one or more and R is as defined above; hereinafter referred to as the “Subject Polymers”, as broad spectrum in vivo antimicrobials and/or anti-cancer agents suitable for treatment by the oral route.
It is known that the rate of passage of molecules across membranes has an inverse relationship to their molecular weights. Thus, it is widely and generally accepted in the art that molecules taken by the oral route and having molecular weight <1000, will have their passage across the gut so restricted, and consequently any potential toxicity will be effectively minimized.
The Subject Polymers, being aldehydic, are especially reactive with protein. (In fact, in microbiological assays, the routine and facile method of quenching/destroying the activity of the Subject Polymers is to add protein.) Hence, the Subject Polymers would not be expected to exhibit significant microbiological activity in the intestine, especially in the presence of proteinaceous feed.
Therefore, the present invention provides a method of prevention and/or treatment of gastrointestinal disease in humans, animals or birds resulting from the microbial infection of the gastrointestinal tract, and a method for increasing weight gain in humans, animals or birds having gastrointestinal disease and/or infection, comprising administering an effective amount to said humans, animals or birds of a pharmaceutical composition or feed additive, comprising an effective amount of the Subject Polymers together with a pharmaceutically or veterinarally acceptable carrier, diluent, adjuvant, excipient or controlled release system.